More than 50 years ago, vitamin A was recognized as an important nutritional factor in the calcification process of bones and teeth. Deficiency of vitamin A has been associated with severe malformations of bones characterized by an increase in their thickness and alterations of their normal structure and morphology. Teeth are also affected, particularly enamel and dentin, due to the atrophy and metaplasia of ameloblasts and odontoblasts deficient in vitamin A. This proposal describes the approaches used to evaluate in a fully defined animal model system the biochemical effects of vitamin A deficiency in bone formation through the uptake of various radioactively labeled precursors and metabolites in a tissue culture system. Particular emphasis will be made in studying the effects of vitamin A in the metabolism of sulfated glycosaminoglycans of bones and teeth, as our previous work indicates these to be one of the matrix components affected by the nutritional deficiency. The effect of vitamin A deficiency on developing teeth will also be investigated with a view to evaluating their structure and composition and the susceptibility to dental caries. The underlying hypothesis of this proposal is that vitamin A is essential to the calcification process of bones and teeth and that there is a critical time when this vitamin has to be available to allow normal calcification of mineralized tissues and to confer resistance to various disease stresses. Vitamin A has been found to be lacking in the diets of young children both abroad and in the U.S.A. In view of widespread deficiency of vitamin A in children who have not completed their dental and craniofacial development the biochemical role of vitamin A in calcification should be elucidated.